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آدم سميث : مقدمة موجزة
يتحدث هذا الكتاب عن آدم سميث حيث أن رغم شهرة آدم سميث فإنه ما زال هناك جهل شائع بحجم إنجازاته وإسهاماته في الاقتصاد والسياسة والفلسفة وفي هذه المقدمة الموجزة يقدم د. إيمون باتلر مقدمة بارعة عن حياة آدم سميث على المستويين الشخصي والعملي لم يكتف بدراسة كتابه «ثروة الأمم» بكل ما فيه من أفكار لامعة حول التجارة وتقسيم العمل بل تطرق أيضا إلى بحث مؤلفات وأعمال له أقل شهرة مثل كتاب «نظرية المشاعر الأخلاقية» والمحاضرات التي ألقاها على الطلاب والباحثين إضافة إلى كتاباته حول تاريخ العلوم وبذلك يستعرض لنا باتلر إنجازات آدم سميث الفكرية استعراضا شاملا ودقيقا.
BOOK
The Fourth Industrial Revolution and education
The inauguration of one of the world’s leading specialists in artificial intelligence (AI) as the Vice Chancellor of a South African university has brought the Fourth Industrial Revolution to the fore in the local media – and raised interest in what the Fourth Industrial Revolution might mean for education in general – and for post-school education in particular. A fusion of technologies that is blurring the lines between the physical, digital and biological domains, AI’s precise beginning is not clear, but it was certainly in evidence 3 years ago, if not earlier, building on the digital revolution.
Journal Article
Classification and Personalized Prognosis in Myeloproliferative Neoplasms
Genetic analysis involving 2035 patients with a myeloproliferative disorder identified eight genomic subgroups with distinct clinical phenotypes, risk of leukemic transformation, and event-free survival.
Journal Article
Reflections of an Editor-in-Chief: 2013-2019
The year 2013 and those that followed were a time during which several important changes were made to the nature and operation of the Journal. The changes were the result of teamwork, of considerable discussion and, when needed, of research on the part of the team. Susan Veldsman was often consulted, and when required, some matters were referred to the Editorial Advisory Board. But in all cases, these developments were the result of thorough joint discussion. The changes mentioned are not in any specific order. Important amongst them, however, is the issue of gender: over the almost seven years of my editorship, the number of women scholars who were Associate Editors increased from one of ten to seven of ten, while membership of the Editorial Advisory Board progressed from one woman amongst five to three amongst six. The position of Associate Editor Mentee was introduced in 2018, with three of the four mentees appointed in the first year (2018/2019) being young women. Of equal importance to the Journal's stature and recognition, and equally important for the scholars submitting their research to the Journal, was the change in the measure of international impact, the so-called impact factor.
Journal Article
Convergent somatic mutations in metabolism genes in chronic liver disease
The progression of chronic liver disease to hepatocellular carcinoma is caused by the acquisition of somatic mutations that affect 20–30 cancer genes
1
–
8
. Burdens of somatic mutations are higher and clonal expansions larger in chronic liver disease
9
–
13
than in normal liver
13
–
16
, which enables positive selection to shape the genomic landscape
9
–
13
. Here we analysed somatic mutations from 1,590 genomes across 34 liver samples, including healthy controls, alcohol-related liver disease and non-alcoholic fatty liver disease. Seven of the 29 patients with liver disease had mutations in
FOXO1
, the major transcription factor in insulin signalling. These mutations affected a single hotspot within the gene, impairing the insulin-mediated nuclear export of FOXO1. Notably, six of the seven patients with
FOXO1
S22W
hotspot mutations showed convergent evolution, with variants acquired independently by up to nine distinct hepatocyte clones per patient.
CIDEB
, which regulates lipid droplet metabolism in hepatocytes
17
–
19
, and
GPAM
, which produces storage triacylglycerol from free fatty acids
20
,
21
, also had a significant excess of mutations. We again observed frequent convergent evolution: up to fourteen independent clones per patient with
CIDEB
mutations and up to seven clones per patient with
GPAM
mutations. Mutations in metabolism genes were distributed across multiple anatomical segments of the liver, increased clone size and were seen in both alcohol-related liver disease and non-alcoholic fatty liver disease, but rarely in hepatocellular carcinoma. Master regulators of metabolic pathways are a frequent target of convergent somatic mutation in alcohol-related and non-alcoholic fatty liver disease.
Whole-genome sequencing analysis of somatic mutations in liver samples from patients with chronic liver disease identifies driver mutations in metabolism-related genes such as
FOXO1
, and shows that these variants frequently exhibit convergent evolution.
Journal Article
Genomic Classification and Prognosis in Acute Myeloid Leukemia
The authors identify 11 discrete genetic subsets of acute myeloid leukemia on the basis of the expression and coexpression of particular mutations. Prospective studies may elucidate distinct approaches to their management.
Acute myeloid leukemia (AML) is characterized by clonal expansion of undifferentiated myeloid precursors, resulting in impaired hematopoiesis and bone marrow failure. Although many patients with AML have a response to induction chemotherapy, refractory disease is common, and relapse represents the major cause of treatment failure.
1
Cancer develops from somatically acquired driver mutations, which account for the myriad biologic and clinical complexities of the disease. A classification of cancers that is based on causality is likely to be durable, reproducible, and clinically relevant. This is already evident in the case of AML, for which there has been a progressive shift from . . .
Journal Article
Heterogeneity of genomic evolution and mutational profiles in multiple myeloma
Multiple myeloma is an incurable plasma cell malignancy with a complex and incompletely understood molecular pathogenesis. Here we use whole-exome sequencing, copy-number profiling and cytogenetics to analyse 84 myeloma samples. Most cases have a complex subclonal structure and show clusters of subclonal variants, including subclonal driver mutations. Serial sampling reveals diverse patterns of clonal evolution, including linear evolution, differential clonal response and branching evolution. Diverse processes contribute to the mutational repertoire, including
kataegis
and somatic hypermutation, and their relative contribution changes over time. We find heterogeneity of mutational spectrum across samples, with few recurrent genes. We identify new candidate genes, including truncations of
SP140
,
LTB, ROBO1
and clustered missense mutations in
EGR1
. The myeloma genome is heterogeneous across the cohort, and exhibits diversity in clonal admixture and in dynamics of evolution, which may impact prognostic stratification, therapeutic approaches and assessment of disease response to treatment.
Multiple myeloma is a malignant plasma cell disorder with a complex molecular pathogenesis. Here, the authors perform whole-exome sequencing, copy-number profiling and cytogenetic analysis in 84 myeloma samples and highlight the diversity and evolution of the mutational profile underlying the disease.
Journal Article
Signatures of mutational processes in human cancer
All cancers are caused by somatic mutations; however, understanding of the biological processes generating these mutations is limited. The catalogue of somatic mutations from a cancer genome bears the signatures of the mutational processes that have been operative. Here we analysed 4,938,362 mutations from 7,042 cancers and extracted more than 20 distinct mutational signatures. Some are present in many cancer types, notably a signature attributed to the APOBEC family of cytidine deaminases, whereas others are confined to a single cancer class. Certain signatures are associated with age of the patient at cancer diagnosis, known mutagenic exposures or defects in DNA maintenance, but many are of cryptic origin. In addition to these genome-wide mutational signatures, hypermutation localized to small genomic regions, ‘kataegis’, is found in many cancer types. The results reveal the diversity of mutational processes underlying the development of cancer, with potential implications for understanding of cancer aetiology, prevention and therapy.
An analysis of mutations from over 7,000 cancers of diverse origins reveals the diversity of mutational processes underlying the development of cancer; more than 20 distinct mutational signatures are described, some of which are present in many cancer types, notably a signature attributed to the APOBEC family of cytidine deaminases, whereas others are specific to individual tumour types.
Cancer mutations are a mixed bag
Despite the fact that all cancers are thought to result from somatic mutation — mutations in any cell in the body excluding the germ cells — relatively little is known about the processes of mutation involved. This study analyses almost 5 million mutations from more than 7,000 cancers and demonstrates more than 20 distinct cancer-associated mutational signatures. Some of these signatures are present in many cancers, notably a signature attributed to the APOBEC family of cytidine deaminases, whereas others are specific to individual tumour types. Some signatures are associated with age, known mutagenic exposures or defects in DNA maintenance, but many are of cryptic origin. These findings have potential implications for the understanding of cancer aetiology, prevention and therapy.
Journal Article
Recurrent mutation of IGF signalling genes and distinct patterns of genomic rearrangement in osteosarcoma
Osteosarcoma is a primary malignancy of bone that affects children and adults. Here, we present the largest sequencing study of osteosarcoma to date, comprising 112 childhood and adult tumours encompassing all major histological subtypes. A key finding of our study is the identification of mutations in insulin-like growth factor (IGF) signalling genes in 8/112 (7%) of cases. We validate this observation using fluorescence
in situ
hybridization (FISH) in an additional 87 osteosarcomas, with IGF1 receptor (
IGF1R
) amplification observed in 14% of tumours. These findings may inform patient selection in future trials of IGF1R inhibitors in osteosarcoma. Analysing patterns of mutation, we identify distinct rearrangement profiles including a process characterized by chromothripsis and amplification. This process operates recurrently at discrete genomic regions and generates driver mutations. It may represent an age-independent mutational mechanism that contributes to the development of osteosarcoma in children and adults alike.
Osteosarcoma is a primary malignancy of bone that affects children and adults. Here, the authors sequence childhood and adult osteosarcomas, identifying mutations in insulin-like growth factor signalling genes and distinct genomic rearrangement profiles characterized by chromothripsis-amplification.
Journal Article
Real-Time Auto-Monitoring of Livestock: Quantitative Framework and Challenges
The use of automated sensors has grown rapidly in recent years, with sensor data now routinely used for monitoring in a wide range of situations, including human health and behaviour, the environment, wildlife, and agriculture. Livestock farming is a key area of application, and our primary focus here, but the issues discussed are widely applicable. There is the potential to massively increase the use of empirical data for decision-making in real time, and a range of quantitative methods, including machine learning and statistical methods, have been proposed for this purpose within the literature. In many areas, however, development and validation of quantitative approaches are still needed in order for these methods to effectively inform decision-making. Within the context of livestock farming, for example, it must be practically feasible to repeatedly apply the method dynamically in real time on farms in order to optimise decision-making, and we discuss the challenges in using quantitative approaches for this purpose. It is also crucial to evaluate and compare the applied performance of methods in a fair and robust way—such comparisons are currently lacking within the literature on livestock farming, and we outline approaches to addressing this key gap.
Journal Article